Category Archives: Heart Disease

Paleo Diet and Cardiovascular Disease

Not too many folks eat rabbit these days

A review article in American Journal of Medicine looks at various diets that may have influence on development or progression of cardiovascular disease. All I have is the abstract, which mentions the Paleolithic diet. I don’t have access to the full article. If you do, please leave a comment below regarding the authors’ thoughts on the paleo diet. Among the 25 authors, I recognized three names; two of which are committed vegetarians or vegans (Ornish and Barnard). I suspect the article will be anti-meat.


In cardiology clinic visits, the discussion of optimal dietary patterns for prevention and management of cardiovascular disease is usually very limited. Herein, we explore the benefits and risks of various dietary patterns, including intermittent fasting, low carbohydrate, Paleolithic, whole food plant-based diet, and Mediterranean dietary patterns within the context of cardiovascular disease to empower clinicians with the evidence and information they need to maximally benefit their patients.

Reference: Controversial Dietary Patterns: A High Yield Primer for Clinicians.

Steve Parker, M.D.

Paleo Diet Linked to Cardiovascular Benefits

A score appraising Paleolithic diet and the risk of cardiovascular disease in a Mediterranean prospective cohort


Purpose: To assess the association between a score appraising adherence to the PaleoDiet and the risk of cardiovascular disease (CVD) in a Mediterranean cohort.

Methods: We included 18,210 participants from the Seguimiento Universidad de Navarra (SUN) cohort study. The PaleoDiet score comprised six food groups promoted within this diet (fruit, nuts, vegetables, eggs, meat and fish) and five food groups whose consumption is discouraged (cereals and grains, dairy products, legumes, culinary ingredients, and processed/ultra-processed foods). CVD was defined as acute myocardial infarction with or without ST elevation, non-fatal stroke and cardiovascular death. Cox proportional hazards models adjusted for potential confounders were fitted to assess the association between the PaleoDiet score and CVD risk, and the PaleoDiet and MedDiet indices to explore differences between both diets.

Results: During 12.2 years of follow-up, 165 incident CVD cases were confirmed. A significant inverse association was found between the PaleoDiet score and CVD (HR Q5 vs. Q1: 0.45, 95% CI 0.27-0.76, P for trend = 0.007). A weaker association that became non-significant was observed when the item for low consumption of ultra-processed foods was removed from the score. Joint analysis of PaleoDiet and MedDiet Trichopoulou scores suggested that the inverse association between PaleoDiet and CVD was mainly present when adherence to the MedDiet was also high (HR for high adherence vs low adherence to both diet scores: 0.22, 95% CI 0.08-0.64).

Conclusions: Our findings suggest that the PaleoDiet may have cardiovascular benefits in participants from a Mediterranean country. Avoidance of ultra-processed foods seems to play a key role in this inverse association.

Link to European Journal of Nutrition article.

I was glad to see some new names among the researchers.

Steve Parker, M.D.

PS: If you’ve abandoned your New Years’ diet resolution, consider the Paleobetic Diet!

Does the Paleo Diet Affect Cardiometabolic Risk Factors in Postmenopausal Women?

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You won’t find the answer in the journal article at hand. Probably nobody knows for sure. If you have insomnia, reading the full article (free!) may be cure you temporarily.

Whole-diet interventions and cardiovascular risk factors in postmenopausal women: A systematic review of controlled clinical trials


Objectives: Menopause is accompanied by many metabolic changes, increasing the risk of cardiometabolic diseases. The impact of diet, as a modifiable lifestyle factor, on cardiovascular health in general populations has been well established. The purpose of this systematic review is to summarize the evidence on the effects of whole diet on lipid profile, glycemic indices, and blood pressure in postmenopausal women.

Methods: Embase, Medline, Cochrane Central Register of Controlled Trials, and Google Scholar were searched from inception to February 2021. We included controlled clinical trials in postmenopausal women that assessed the effect of a whole-diet intervention on lipid profile, glycemic indices, and/or blood pressure. The risk of bias in individual studies was assessed using RoB 2 and ROBINS-I tools.

Summary of evidence: Among 2,134 references, 21 trials met all eligibility criteria. Overall, results were heterogenuous and inconsistent. Compared to control diets, some studies showed that participants experienced improvements in total cholesterol (TC), low-density lipoprotein cholesterol (LDL), systolic blood pressure (SBP), fasting blood sugar (FBS), and apolipoprotein A (Apo-A) after following fat-modified diets, but some adverse effects on triglycerides (TG), very low-density lipoprotein cholesterol (VLDL), lipoprotein(a) (Lp(a)), and high-density lipoprotein cholesterol (HDL) concentrations were also observed. A limited number of trials found some effects of the Paleolithic, weight-loss, plant-based, or energy-restricted diets, or of following American Heart Association recommendations on TG, TC, HDL, insulin, FBS, or insulin resistance.

Conclusion: Current evidence suggests that diet may affect levels of some lipid profile markers, glycemic indices, and blood pressure among postmenopausal women. However, due to the large heterogeneity in intervention diets, comparison groups, intervention durations, and population characteristics, findings are inconclusive. Further well-designed clinical trials are needed on dietary interventions to reduce cardiovascular risk in postmenopausal women.

Steve Parker, M.D.

Ultra-Processed Foods Linked to Higher Coronary Artery Disease Risk

Ultra-processed versus processed?

What are ultra-processed foods? I’m not paying $35 for the scientific article to find out. If you can grab the definition from your copy, please share in the Comments section. The 2020 profit from my publishing company was only $937.08, so I’m watching my expenses.

Here’s the free abstract:



Higher ultra-processed food intake has been linked with several cardiometabolic and cardiovascular diseases. However, prospective evidence from US populations remains scarce.


To test the hypothesis that higher intake of ultra-processed foods is associated with higher risk of coronary artery disease.


A total of 13,548 adults aged 45–65 y from the Atherosclerosis Risk in Communities study were included in the analytic sample. Dietary intake data were collected through a 66-item FFQ. Ultra-processed foods were defined using the NOVA classification, and the level of intake (servings/d) was calculated for each participant and divided into quartiles. We used Cox proportional hazards models and restricted cubic splines to assess the association between quartiles of ultra-processed food intake and incident coronary artery disease.


There were 2006 incident coronary artery disease cases documented over a median follow-up of 27 y. Incidence rates were higher in the highest quartile of ultra-processed food intake (70.8 per 10,000 person-y; 95% CI: 65.1, 77.1) compared with the lowest quartile (59.3 per 10,000 person-y; 95% CI: 54.1, 65.0). Participants in the highest compared with lowest quartile of ultra-processed food intake had a 19% higher risk of coronary artery disease (HR: 1.19; 95% CI: 1.05, 1.35) after adjusting for sociodemographic factors and health behaviors. An approximately linear relation was observed between ultra-processed food intake and risk of coronary artery disease.Conclusions

Higher ultra-processed food intake was associated with a higher risk of coronary artery disease among middle-aged US adults. Further prospective studies are needed to confirm these findings and to investigate the mechanisms by which ultra-processed foods may affect health.


I admit I must eat some ultra-processed foods, but I try to limit them.

Heart disease is the #1 killer in the developed world, even more lethal the COVID19! If you haven’t chosen your New Years’ weight-loss diet yet, consider one low in ultra-processed foods, like the paleo diet or Mediterranean diet.

This Shrimp Salad is minimally-processed

Steve Parker, M.D.

High Glycemic Eating Linked to Cardiovascular Disease and Premature Death

Naan, a type of flat bread with a high glycemic index

Haven’t we know this for years? From New England Journal of Medicine:

Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population.


This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause.


In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease.


In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death.

Source: Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality | NEJM

Steve Parker, M.D.

PS: The Paleobetic Diet is low glycemic index, particularly compared with the standard American diet.

Type 2 Diabetes: Major Health Benefit From Drugs That Don’t Cause Hypoglycemia

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A recent study looked at the health benefits of type 2 diabetes drugs, comparing drugs that can cause hypoglycemia and those that don’t. The very first sentence of the abstract didn’t give me much hope for what followed. That sentence was: “Different guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend from the different pharmacological strategies adopted for intensifying glycemic control.” Did you catch the misprint?

This meta-analysis of 13 clinical trials was looking for differences in various health outcomes over the course of at least two years, comparing successful intensive management to standard care or placebo. Successful intensive management was defined as at least a 0.5% (6 mmol/mol) improvement in hemoglobin A1c (HgbA1c) level. “Intensification” of drug therapy is usually applied to a patient who is not at goal HgbA1c level. Undoubtedly, the benefits of intensification will be greater for those at HgbA1c of 10% than for those at 7.5%. BTW, few large clinical trials include patients over 75 years of age.

For my U.S. readers, note that other countries often specify HgbA1c values as mmol/mol instead of %. And blood sugars are not our usual mg/dl, but instead reported as mmol/l. HbA1c of 7% equals 53 mmol/mol, which would indicate and average blood sugar of 154 mg/dl or 8.6 mmol/l. As another example, HbA1c of 6.5% is 48 mmol/mol, reflecting average blood sugar of 140 mg/dl or 7.8 mmol/l. Are you thoroughly confused yet?

In the general population, lowest levels of mortality are seen at HgbA1c’s around 5 to 5.5% (31 to 36.6 mmol/mol). The average healthy non-diabetic adult hemoglobin A1c is 5% (31 mmol/mol) and translates into an average blood sugar of 100 mg/dl (5.56 mmol/l). This will vary a bit from lab to lab. Most healthy non-diabetics would be under 5.7% (38.8 mmol/mol). In December, 2009, the American Diabetes Association established a hemoglobin A1c criterion for the diagnosis of diabetes: 6.5% (47.5 mmol/mol) or higher. Diagnosis of prediabetes involves hemoglobin A1c in the range of 5.7 to 6.4% (38.8 to 46.5 mmol/mol).

Some expert panels recommend aiming for HgbA1c under 7% (53 mmol/mol), others recommend under 6.5% (48 mmol/mol). A major point of debate between the two guideline goals, is that the lower you set the goal, the greater the risk of drug-induced hypoglycemia, which can be lethal. In the early 1980s, the only drugs we had for diabetes were insulin, sulfonylureas, and metformin. Two of those three can can cause hypoglycemia. Now, a majority of our type 2 diabetes drugs don’t cause hypoglycemia.

If you’re at risk for hypoglycemia, teach those you hang with how to recognize and treat it

The Italian researchers did this meta-analysis as part of their effort to produce diabetes drug treatment guidelines for the Italian population. On to the study at hand…

What Did the Researchers Find?

Improved glycemic (blood sugar) control by intensive attention reduced the major cardiovascular event rate by 10% and reduced renal adverse events by 25% but did not affect overall mortality or eye complications.

Intensified therapy with hypoglycemia-inducing drugs did not reduce overall mortality.

Drugs without potential for causing hypoglycemia were linked to lower risk of major cardiovascular events, kidney adverse events, and overall mortality, for HgbA1c under 7% (53 mmol/mol).

In conclusion, the results of this meta-analysis of RCTs show that in people with T2DM the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular complications (major adverse cardiac events and renal adverse events) and all-cause mortality, at least for HbA1c levels above 7%. The reduction of HbA1c below that threshold could have some favorable effects, but there is no available direct evidence in this respect. When the reduction of HbA1c is achieved with drugs inducing hypoglycemia, a progressive reduction of complications and an increase in the risk of severe hypoglycemia is observed. Therefore, the choice of the most adequate HbA1c target for each patient with T2DM should be made considering an appropriate risk/benefit ratio.

Full text in Nutrition, Metabolism & Cardiovascular Diseases.

I think the researchers were particularly glad to find that intensification of drug therapy can reduce risk of heart attack, stroke, kidney complications, and death; all this without the risk of hypoglycemia that comes with drugs like insulin and sulfonylureas. The lack of a mortality benefit from hypoglycemia-inducing drugs may also be important. The benefits of intensive drug therapy (or lack thereof) depend somewhat on the particular complication you’re trying to avoid, and on baseline HgbA1c. Drug therapy is complicated! I expect these researchers would recommend a treatment HgbA1c goal of <7% rather than <6.5%.

Steve Parker, M.D.

PS: Reduce your need for diabetes drugs by losing excess weight, exercising, and eating low-carb.

If You Have Type 2 Diabetes, Coffee May Prolong Your Life

“Is the world shaking, or is it just me?”

Compared to no coffee-drinking, drinking four cups a day reduced overall death rate by 20%, reduced cardiovascular deaths by 40%, and reduced death rate form coronary artery disease by 30%. The study at hand was a meta-analysis involving over 80,000 folks with type 2 diabetes living in multiple studies and followed clinically for 5-20 years. “Cardiovascular deaths” are usually heart attacks, strokes, cardiac arrest, or heart failure.

I vaguely recall a study several decades ago linking coffee to pancreas cancer, one of the deadliest cancers. The research was subsequently discredited.

Is coffee as a drink considered “paleo”? It seems to have originated in Africa, which is considered the cradle of humanity. I’m not sure anybody knows when we started drinking it; maybe 14 centuries ago. It’s possible we chewed it as a stimulant even before that. Extant humans who’ve been drinking four cups a day for many years are unlikely to drop the habit even if it isn’t paleo.

From Nutrition, Metabolism & Cardiovascular Diseases:


To evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.

Data synthesis

PubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.


Drinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.


Steve Parker, M.D.

Finerenone: New Drug to Prevent Chronic Kidney Disease and Cardiovascular Death in Type 2 Diabetes

Verbatim from the FDA press release:

FDA has approved Kerendia (finerenone) tablets to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.

Diabetes is the leading cause of chronic kidney disease and kidney failure in the United States. Chronic kidney disease occurs when the kidneys are damaged and cannot filter blood normally. Because of defective filtering, patients can have complications related to fluid, electrolytes (minerals required for many bodily processes), and waste build-up in the body. Chronic kidney disease sometimes can progress to kidney failure. Patients also are at high risk of heart disease.

The efficacy of Kerendia to improve kidney and heart outcomes was evaluated in a randomized, multicenter, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes. In this study, 5,674 patients were randomly assigned to receive either Kerendia or a placebo.

The study compared the two groups for the number of patients whose disease progressed to a composite (or combined) endpoint that included at least a 40% reduction in kidney function, progression to kidney failure, or kidney death. Results showed that 504 of the 2,833 patients who received Kerendia had at least one of the events in the composite endpoint compared to 600 of the 2,841 patients who received a placebo.

The study also compared the two groups for the number of patients who experienced cardiovascular death, a non-fatal heart attack, non-fatal stroke, or hospitalization for heart failure. Results showed that 367 of the 2,833 patients receiving Kerendia had at least one of the events in the composite endpoint compared to 420 of the 2,841 patients who received a placebo, with the treatment showing a reduction in the risk of cardiovascular death, non-fatal heart attack, and hospitalization for heart failure.

Side effects of Kerendia include hyperkalemia (high levels of potassium), hypotension (low blood pressure), and hyponatremia (low levels of sodium). Patients with adrenal insufficiency (when the body does not produce enough of certain hormones) and those receiving simultaneous treatment with strong CYP3A4 inhibitors should not take Kerendia.

Kerendia received priority review and fast track designations for this application.

FDA granted the approval of Kerendia to Bayer Healthcare.

Click for prescribing information.

Parker here.

Just offhand, finerenone doesn’t look like a great drug. Helpful, maybe. Chronic kidney disease can end up at ESRD (end stage renal disease), which requires thrice weekly hemodialysis if the patient wants to stay alive. (Yes, peritoneal dialysis is an alternative.) Preventing ESRD is an incredible benefit for an individual.

Finerenone seems to be a well-tolerated daily pill. The main adverse effect is elevated blood potassium level, which can cause palpitations, and death infrequently. Less commonly, the drug can cause low blood pressure.

The ultimate role of finerenone in our armamentarium against disease and suffering will probably depend on cost and the number needed to treat.

Steve Parker, M.D.

Dietary Salt Restriction Lowers Blood Pressure in Type 2 Diabetes

A pinch of salt may cut the bitterness in a cup of coffee

Yes, according to an article in Nutrition, Metabolism & Cardiovascular Disease. The systolic pressure lowering is 5-6 points, but only 1-2 points on average for diastolic pressure. This degree of BP lowering is not dramatic, but might prevent an escalation of antihypertensive drug dosing or initiation of an additional drug.

Steve Parker, M.D.

Paleo Diet Effect on Athletes

hunter, hunting, prehistoric, paleo diet, caveman, saber-toothed tiger, cavewoman

Judging from the article abstract below, it looks like the researchers didn’t find any major impact of the paleo diet on athletic performance, compared to “healthy” control diets. The title of the scientific report is “Paleolithic Diet-Effect on the Health Status and Performance of Athletes?” That sure made me think they were going to look at athletic performance. Here’s one of two sentences in the abstract that refer to athletic performance: “Lower positive impact of paleo diet on performance was observed it the group without exercise.” What does that even mean? Looks like even scientific journals are using click-bait now.

Before you read the abstract, remember that higher blood triglycerides, total cholesterol, and LDL cholesterol are linked in some studies to cardiovascular disease. Also, lower plasma glucose (sugar) and insulin levels are linked in some studies to less risk of cardiovascular disease. So the paleo diet may be healthful since it shifts those numbers in the right direction.

The aim of this meta-analysis was to review the impact of a Paleolithic diet (PD) on selected health indicators (body composition, lipid profile, blood pressure, and carbohydrate metabolism) in the short and long term of nutrition intervention in healthy and unhealthy adults. A systematic review of randomized controlled trials of 21 full-text original human studies was conducted. Both the PD and a variety of healthy diets (control diets (CDs)) caused reduction in anthropometric parameters, both in the short and long term. For many indicators, such as weight (body mass (BM)), body mass index (BMI), and waist circumference (WC), impact was stronger and especially found in the short term. All diets caused a decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), albeit the impact of PD was stronger. Among long-term studies, only PD cased a decline in TC and LDL-C. Impact on blood pressure was observed mainly in the short term. PD caused a decrease in fasting plasma (fP) glucose, fP insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) in the short run, contrary to CD. In the long term, only PD caused a decrease in fP glucose and fP insulin. Lower positive impact of PD on performance was observed in the group without exercise. Positive effects of the PD on health and the lack of experiments among professional athletes require longer-term interventions to determine the effect of the Paleo diet on athletic performance.


Click for the full text article. The article title and abstract were so poorly written that I’m not wasting time on the full text. Let me know if you find anything interesting. Furthermore, this “research” was a meta-analysis, so I’m even more skeptical about any conclusions on athletic performance.

Steve Parker, M.D.